Blood Based Biomarkers: Where Are We Going?

Howard Fillit, MDExecutive Director and Chief Science OfficerThe Alzheimer’s Drug Discovery Foundation

Intended Uses of Biomarkers

• Research: understanding factors in pathogenesis, identifying and validating new drug targets in preclinical and early clinical research

• Diagnosis: the identification of the presence of Alzheimer’s disease (eg. PET amyloid imaging) for early detection and identification of patients for clinical trials

 

• Screening: enabling intervention at an earlier and potentially more curable stage than under usual clinical diagnostic conditions (eg. cognitive function, blood based biomarkers)

• Monitoring response during therapy, with potential for adjusting level of intervention (a pharmacodynamic marker; eg. FDG-PET, CSF beta-amyloid/tau)

• Risk prediction: identifying subpopulations who may respond to a treatment, and leading to preventive interventions for those at sufficient risk (eg. apoE testing)

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Use of Biomarkers for Clinical Development in Alzheimer’s Disease

• Efficacy response biomarker

– may substitute for clinical response, making clinical trials more efficient, less costly

– may be target specific

– “Qualified biomarkers” used in FDA regulatory approval as supporting data for indication

– Once validated by FDA, surrogate markers may be used in regulatory approval

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What is a Surrogate Marker?

• A biomarker intended to substitute for a clinical endpoint in clinical trials and regulatory approval (eg. Cholesterol)

• A surrogate endpoint is expected to predict clinical benefit (or harm, or lack of benefit) based on epidemiologic, therapeutic, pathophysiologic and other scientific evidence

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http://www.fda.gov/downloads/Drugs/NewsEvents/UCM300734.pdf

6http://www.fda.gov/downloads/Drugs/NewsEvents/UCM300734.pdf

Some Issues in Biomarker Development

• Standardization and replication of assays• Clinical study design

– Lack of a priori hypothesis testing– Inadequate power, small sample sizes– Failure to account for co-morbidities– Exploratory studies often not confirmed in validation samples– No effective therapies to validate use– Publication bias

• Can a blood-based biomarker be developed for Alzheimer’s disease, or any neurodegenerative disease?

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